Developing the QSPR model for predicting the storage lipid/water distribution coefficient of organic compounds

Abstract

• A predictive model for storage lipid/water distribution coefficient was developed.

• The model yields outstanding fitting performance, robustness, and predictive ability.

• Hydrophobic and electrostatic interactions and molecular size dominate log K_lip/w.

• The model can be used in a wide application domain to predict log K_lip/w values.

The distribution of organic compounds in stored lipids affects their migration, transformation, bioaccumulation, and toxicity in organisms. The storage lipid/water distribution coefficient (log K_lip/w) of organic chemicals, which quantitatively determines such distribution, has become a key parameter to assist their ecological security and health risk. Due to the impossibility to measure K_lip/w values for a huge amount of chemicals, it is necessary to develop predictive approaches. In this work, a quantitative structure-property relationship (QSPR) model for estimating log K_lip/w values of small organic compounds was constructed based on 305 experimental log K_lip/w values. Quantum chemical descriptors and n-octanol/water partitioning coefficient were employed to characterize the intermolecular interactions that dominate log K_lip/w values. The hydrophobic and electrostatic interactions and molecular size have been found to play important roles in governing the distribution of chemicals between lipids and aqueous phases. The regression (R² = 0.959) and validation (Q² = 0.960) results indicate good fitting performance and robustness of the developed model. A comparison with the predictive performance of other commercial software further proves the higher accuracy and stronger predictive ability of the developed K_lip/w predictive model. Thus, it can be used to predict the K_lip/w values of cycloalkanes, long-chain alkanes, halides (with fluorine, chlorine, and bromine as substituents), esters (without phosphate groups), alcohols (without methoxy groups), and aromatic compounds.

Graphical abstract

Keywords

Storage lipid/water distribution coefficient / log K _lip/w / Organic compounds / QSPR / Quantum chemical descriptors

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